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Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion

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Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion. / Clark, Danielle J; McMillan, Laura E; Tan, Sin Lih; Bellomo, Gaia; Massoue, Clementine; Thompson, Harry; Mykhaylechko, Lidiya ; Alibhai, Dominic; Ruan, Xiongtao; Singleton, Kentner L; Du, Minna ; Hedges, Alan; Schwartzberg, Pamela L; Verkade, Paul; Murphy, Robert F; Wuellfing, Christoph.

In: eLife, Vol. 8, 24.10.2019.

Research output: Contribution to journalArticle

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Clark, DJ, McMillan, LE, Tan, SL, Bellomo, G, Massoue, C, Thompson, H, Mykhaylechko, L, Alibhai, D, Ruan, X, Singleton, KL, Du, M, Hedges, A, Schwartzberg, PL, Verkade, P, Murphy, RF & Wuellfing, C 2019, 'Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion', eLife, vol. 8. https://doi.org/10.7554/eLife.45789

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Clark, Danielle J ; McMillan, Laura E ; Tan, Sin Lih ; Bellomo, Gaia ; Massoue, Clementine ; Thompson, Harry ; Mykhaylechko, Lidiya ; Alibhai, Dominic ; Ruan, Xiongtao ; Singleton, Kentner L ; Du, Minna ; Hedges, Alan ; Schwartzberg, Pamela L ; Verkade, Paul ; Murphy, Robert F ; Wuellfing, Christoph. / Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion. In: eLife. 2019 ; Vol. 8.

Bibtex

@article{fcd0794f3d1a414ebfae6181ba720761,
title = "Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion",
abstract = "Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen-presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5 µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.",
author = "Clark, {Danielle J} and McMillan, {Laura E} and Tan, {Sin Lih} and Gaia Bellomo and Clementine Massoue and Harry Thompson and Lidiya Mykhaylechko and Dominic Alibhai and Xiongtao Ruan and Singleton, {Kentner L} and Minna Du and Alan Hedges and Schwartzberg, {Pamela L} and Paul Verkade and Murphy, {Robert F} and Christoph Wuellfing",
year = "2019",
month = "10",
day = "24",
doi = "10.7554/eLife.45789",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Transient protein accumulation at the center of the T cell antigen-presenting cell interface drives efficient IL-2 secretion

AU - Clark, Danielle J

AU - McMillan, Laura E

AU - Tan, Sin Lih

AU - Bellomo, Gaia

AU - Massoue, Clementine

AU - Thompson, Harry

AU - Mykhaylechko, Lidiya

AU - Alibhai, Dominic

AU - Ruan, Xiongtao

AU - Singleton, Kentner L

AU - Du, Minna

AU - Hedges, Alan

AU - Schwartzberg, Pamela L

AU - Verkade, Paul

AU - Murphy, Robert F

AU - Wuellfing, Christoph

PY - 2019/10/24

Y1 - 2019/10/24

N2 - Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen-presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5 µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.

AB - Supramolecular signaling assemblies are of interest for their unique signaling properties. A µm scale signaling assembly, the central supramolecular signaling cluster (cSMAC), forms at the center of the interface of T cells activated by antigen-presenting cells. We have determined that it is composed of multiple complexes of a supramolecular volume of up to 0.5 µm3 and associated with extensive membrane undulations. To determine cSMAC function, we have systematically manipulated the localization of three adaptor proteins, LAT, SLP-76, and Grb2. cSMAC localization varied between the adaptors and was diminished upon blockade of the costimulatory receptor CD28 and deficiency of the signal amplifying kinase Itk. Reconstitution of cSMAC localization restored IL-2 secretion which is a key T cell effector function as dependent on reconstitution dynamics. Our data suggest that the cSMAC enhances early signaling by facilitating signaling interactions and attenuates signaling thereafter through sequestration of a more limited set of signaling intermediates.

U2 - 10.7554/eLife.45789

DO - 10.7554/eLife.45789

M3 - Article

C2 - 31663508

VL - 8

JO - eLife

JF - eLife

SN - 2050-084X

ER -